This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years of age. The macula, the specialized area of the retina that underlies sharp central vision, is present only in human and nonhuman primates, so that only nonhuman primates can provide an accurate model for this complex disease. Furthermore, both rhesus and Japanese macaques develop syndromes closely resembling human AMD, and in rhesus we have confirmed two genetic risk factors that are shared with humans. Availability of thesenonhuman primate models of AMD makes possible tests of several promising therapeutic approaches, including gene therapy, stem cell therapy, growth factors and nutritional interventions, as well as studies of the mechanisms underlying retinal degeneration. This project's objective is to continue to characterize these models using several complementary approaches: 1) identifying monkeys with naturally-occurring macular disease in the ONPRC macaque colonies;2) determining the genetic mutations or susceptibility factors and gene expression changes underlying this disease;3) testing the feasibility, safety and efficacy of retinal gene therapies and stem cell therapies;and 4) testing the effects of long-term, controlled dietary interventions that may protect the macula from macular degeneration. Studies in the past year continued the work of defining genetic factors, tested the feasibility and safety of both gene and stem cell therapies, and characterized changes in retinal function in monkeys lacking dietary xanthophylls and n-3 fatty acids, two nutrients thought to lower the risk of AMD.